The long-term objectives of this project are 1) to identify functional networks of cortical areas in the human brain that subserve visual spatial attention, and 2) to determine the effects of manipulation of synaptic levels of acetylcholine on the physiology of these functional networks. Humans employ spatial attention to select portions of the visual field that are most relevant for their current behavioral goals. If a visual stimulus appears in an attended location, observers perceive the stimulus more accurately than if the same stimulus is presented to an unattended location. This improvement in perception is thought to be due to attention signals that are transmitted by parietal cortex to early visual cortical areas. However, the neural pathways that carry these attention signals to visual cortex are largely unknown. Acetylcholine is a neurotransmitter that plays an important role in attention networks in the brain. Drugs that prolong the synaptic actions of endogenous acetylcholine (cholinesterase inhibitors) improve performance on attention tasks in human subjects. However, very little is known regarding the physiological effects of acetylcholine on attention signals. The fundamental importance of attention for behavior is demonstrated by the many brain disorders characterized by compromised attention networks. Attention abnormalities are the central symptom in Attention Deficit Disorder. Additionally, many of the mental impairments that have been associated with Alzheimer's disease can be traced to a failure of attention. We will use neuroimaging (functional magnetic resonance imaging, or fMRI) to measure the activity in defined brain areas while subjects are performing attention-demanding tasks. Changes in activity in these areas during task performance will be compared across the identified brain areas, using coherency and partial coherency methods recently developed by our group, to characterize attention pathways and flow of attention signals to visual cortex. In addition, subjects will be administered donepezil (trade name: Aricept), a cholinesterase inhibitor and Alzheimer's medication that enhances attention. The effects of this drug on the functional networks underlying attention will be measured. PUBLIC HEALTH RELEVANCE We will use magnetic resonance imaging (MRI) to measure brain activity in healthy human subjects while they are maintaining attention at a defined visual location. The activity in many brain areas will be compared to identify the network of brain regions that is responsible for visual attention. In addition, the subjects will be administered donepezil, an Alzheimer's medication known to improve attention, and we will measure the effects of this drug on brain activity and the communication between brain areas during sustained attention.